Device for the application of surgical materials to tissue

ABSTRACT

The invention relates to a device comprising a surgical material and a support material and related methods for the application of the surgical material to a wound or surgical site using the device.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/850,025, filed Sep. 10, 2015, which claims priority to U.S.Application No. 62/049,835, filed Sep. 12, 2014 and to U.S. ApplicationNo. 62/048,597, filed Sep. 10, 2014, each of which is incorporated byreference herein in its entirety.

FIELD OF THE INVENTION

The present invention relates to surgical devices and related methodsfor tissue repair.

BACKGROUND OF THE INVENTION

Bone hemostatic materials are either wax-like, putty-like, or paste-likein consistency. Waxlike materials such as bone wax and Ostene™ must bewarmed and kneaded to soften them into a putty-like consistency forapplication to bleeding bone. Other commercially available putty-likehemostatic materials such as Hemasorb™, Hemasorb Plus™, and AbsorbableHemostatic Bone Putty (AHBP™) do not require warming or kneading priorto application to bone.

When the bleeding bone surface is elongated and narrow such as themedially-divided sternum, application of hemostatic materials usingconventional surgical manipulation is more difficult. The presentinvention addresses the need to provide a more effective means forapplying hemostatic and other, e.g., antimicrobial, putty-like materialsto the surface of bleeding bone during a surgical procedure.

A new construct concept has been developed to provide a more surgicallyconvenient method for applying hemostatic and drug-containing materialsto bleeding surfaces. This concept can be applied to surfaces of anyanatomical dimension. Another advantage of this construct is that it mayoffer protection from damage to surgical gloves by sharp bone surfaces.

SUMMARY OF THE INVENTION

The invention relates to a device comprising a surgical material and asupport material and related methods for the application of the surgicalmaterial to a wound or surgical site using the device. In one aspect,the device comprises the surgical material in the form of a ribbon orsheet contained between two layers of the support material (e.g., a toplayer and a bottom layer). In one aspect, the two layers of the supportmaterial are not in contact with each other. The device may be of anysuitable length to width ratio and is adapted to be cut using commonsurgical instruments into an appropriate sized segment or shape forapplication to a wound surface or surgical site. The size of theappropriate sized segment or shape will depend upon the geometry of thewound or surgical site. The device is flexible and can be folded. Thesupport material is non-adhesive to surgical gloves so that the devicecan be manipulated with gloved hands without adhering to the gloves.Thus, alternatively, or in addition to cutting, the device maybe foldedinto an appropriate sized segment or shape for application to a woundsurface or surgical site.

The support material may be constructed from body-absorbable ornon-absorbable components, or it may comprise a mixture ofbody-absorbable and non-absorbable components. Each layer of the supportmaterial may be made of the same or different material. The supportmaterial maybe dyed or pigmented, or it may be uncolored. The supportmaterial may be in the form of a mesh. The mesh may be a microporousmesh, having pore sizes of less than 10 microns; or the mesh may be amacroporous mesh, having pore sizes of greater than 75 microns.Preferably, for hard tissue applications, the support material isbody-absorbable.

In one aspect, the support material is constructed from a synthetic ornatural absorbable polymer, e.g., polyglycolic acid, polylactic acid,copolymers of lactic and glycolic acids, collagen, cross-linked alginicacid, etc.

In one embodiment, the support material is a fabric material comprisingbody-absorbable and non-absorbable components. In one embodiment, thebody-absorbable component of the fabric material comprises or consistsof fibers of polyglycolic acid or polydioxanone, or a mixture of thetwo. In one embodiment, the non-absorbable component of the fabricmaterial comprises or consists of fibers of, for example, polypropylene,polyethylene terephthalate or nylon, or a mixture of the latter two. Thefabric material can be prepared from monofilament or multifilamentfibers in varying fiber densities and may be flat-bed or circularlyknitted or woven or non-woven in construction. Knitted fabrics arepreferred to woven because they are less prone to fraying, if cut.

In one embodiment, the fabric material is knitted or woven frommonofilament or multifilament fiber. The physical characteristics of thefabric are controlled primarily by the denier, tenacity and modulus ofthe fiber and the density and geometry of the knit or weaveconstructions. The fiber may be absorbable, e.g., polyglycolic acidmultifilament or polydioxanone monofilament, or it may benon-absorbable, e.g., polyethylene terephthalate multifilament or nylonor polypropylene monofilament.

In one embodiment, the fabric material consists of a non-woven polymerfabric. In one aspect, the non-woven polymer fabric comprises orconsists of a non-absorbable polymer such as Tyvek™ (DuPont) which isspun-bonded high density polyethylene. In another aspect, the non-wovenpolymer fabric is body-absorbable.

In another embodiment, the support material is a film. The film may becontinuous or appropriately fenestrated. Film thickness maybe determinedby the modulus of the polymer employed, i.e., the higher the modulus,the thinner the film can be made. Further, to prevent the surgicalmaterial from sticking to the film, the film can be prepared from apolymer or a polymer mixture having a low surface energy, e.g.,poly(propylene), poly(tetrafluoroethylene) or a silicone polymer (apolyalkylsiloxane).

In one embodiment, the surgical material is in the form of a puttyhaving a viscosity of from of from 250,000-100,000,000 (cP at 20 C) andmay be, for example, a hemostatic material, a bone void filler, a bonegraft extender, a bone cement, or an antimicrobial, analgesic,antineoplastic, anti-inflammatory, radiopaque, osteoconductive and/orosteoinductive material. In one embodiment, the surgical material is aputty or paste, for example as represented by the tradenames Hemasorb™,Hemasorb Plus™, and Absorbable Hemostatic Bone Putty (AHBP™).

In one aspect, the surgical material is a putty that acts as amechanical hemostat when applied to the bleeding surface of hard or softtissue. The term mechanical hemostat is meant to convey a material thatis effective to stop bleeding without the use of chemical agents, e.g.,pro-coagulants. Mechanical hemostasis or tamponade refers tomechanically blocking the bleeding pores or canals of the cut or damagedbone to arrest hemorrhage. This is distinguished from chemicalhemostasis which utilizes chemical means to promote the clotting ofblood.

In one embodiment, the device is particularly adapted for application ofsurgical pastes and putties to hard tissues, such as cut bone orcartilage. In one aspect of the methods described herein, the device isused to apply the surgical material to at least one surface of a wound,or to a surgical site. In one aspect, the method is a method forhemostasis of actively bleeding hard tissue, such as bone, the methodcomprising removing one layer of a support material to expose onesurface of a hemostatic surgical material, applying the exposed surfaceof the hemostatic material to at least one surface of the bleeding boneby pressing the exposed surface of the surgical material onto thesurface of the hard tissue until it adheres to the bone tissue, and thenremoving the second layer of support material from the surgicalmaterial.

In another aspect, the device is used in a method for removing unwantedsurgical material from a wound or surgical site. This is accomplished byremoving the support material and, with it, the adhering, unwantedsurgical material to be discarded.

In one aspect, the device is used in a method for providing mechanicalhemostasis to a wound or surgical site by applying the hemostaticmaterial to at least one surface of the wound, or to the surgical site,which maybe actively bleeding. In some surgical procedures, the devicemaybe used to apply the hemostatic material to at least two surfaces ofthe wound, such as two surfaces of a cut bone, thereby providingmechanical hemostasis at one or more bleeding surfaces of the wound orat the surgical site.

In one embodiment, the device is in the form of an elongated ribbonsuitable for use on sternum edges, skull flap edges, and at the site ofreapproximated tissues.

In another embodiment, the device is in the form of sheet in the shapeof a square or rectangle. In this form, the device can be cut into anydesired shape and size and wrapped around tissues or blood vessels or beplaced on or between tissue surfaces.

The surgical advantages of the present device relate to its ability tobe cut and/or folded into a preferred shape that adheres to itself and,wrapped in one or more layers on or around a bleeding surface, adheresto either or both the wound surface and/or itself (similar to thegeometry of a sphygmomanometer cuff) to provide various thicknesses andshapes to accommodate different anatomical surfaces and degrees ofbleeding severity.

The device maybe manufactured, for example, by producing a putty-likeribbon of the hemostatic material, optionally by extrusion through adie, and placing the hemostatic material between two layers of thesupport material.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: a ball prepared from a strip of fabric-putty laminate, 2 shows atwisted ribbon of fabric-putty laminate and 3 shows several layers of afabric-putty laminate strip wrapped around a gloved finger.

FIG. 2: an extruded strip of surgical material (e.g., hemostatic putty)sandwiched between two layers of knitted, pigmented polypropylenefabric.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to a device that provides mechanical assistancefor the application of surgical materials to a wound or surgical site.The device comprises a surgical material and one or two layers of asupport material. The surgical material is typically in the form of alayer of putty or paste and the support material is typically in theform of a mesh or film layer. A layer of surgical material is typicallyin the range of 0.1 to 5 cm thick, preferably about 0.1 to 0.5 cm thick,and the mesh or film layer may be in the range of about 0.1 to 0.6 mmthick, preferably about 0.3 mm, 0.4 mm, or 0.5 mm thick. The mesh may bea microporous mesh, having pore sizes of less than 10 microns; or themesh may be a macroporous mesh, having pore sizes of greater than 75microns. The support material may be body-absorbable or non-absorbable.The surgical material may also be body-absorbable or non-absorbable. Thedevice can be cut into any desired shape or size, for example to wrap itaround blood vessels or cut tissue. In one embodiment, the device is inthe form of an elongated ribbon suitable for use on sternum edges, skullflap edges, and at the site of reapproximated tissues. In anotherembodiment, the device is in the form of sheet in the shape of a squareor rectangle.

In one embodiment the surgical material is a high viscosity material,e.g., a material having a viscosity in the range of 250,000-100,000,000(cP at 20 C). Surgical materials in this range of viscosity are suitablefor hard tissue (e.g., bone, cartilage) applications. In a particularembodiment, the surgical material is in the form of a putty having aviscosity of from of from 250,000-100,000,000 (cP at 20 C). The term“putty” refers to a composition that is soft, moldable, preferablynon-elastic, and cohesive. In one aspect, the surgical material is inthe form of a putty that is moldable by hand at room temperature.Suitable surgical putties are described, for example, in WO 201303652and U.S. Ser. No. 14/553,847, each of which is incorporated herein byreference in its entirety.

In another embodiment, the surgical material has a viscosity in therange of 1000-250,000 (cP at 20 C). Surgical materials in this range ofviscosity are suitable for soft tissue applications. Thus, for softtissue applications the surgical material is generally of a lowerviscosity and may be in the form of a soft putty, gel or paste.Typically for soft tissue applications the support material is the formof a non-body absorbable mesh or film.

The device is typically manufactured as a ribbon or sheet of at leastone layer of a support material and at least one layer of a surgicalmaterial. But the device may be cut or manipulated into differentshapes. In one embodiment, the device is in the form of a ribbon orsheet. In another embodiment, the device is in the form of a square,rectangle, circle, or cylinder.

In one embodiment, a single layer of surgical material is containedbetween two layers of a support material. In one embodiment, the devicecontains only one layer of support material and one layer of surgicalmaterial in contact with one surface of the support material. In anotherembodiment, a single layer of support material is between two layers ofthe surgical material.

In one embodiment, the surgical material forms a continuous surface incontact with a surface of at least one layer of support material. Inanother embodiment, the surgical material is in the form of dropletsspaced at a controlled or variable distance from each other on a surfaceof at least one layer of support material. In one embodiment, thedroplets are spaced at a distance of from about ⅛ inch to 3 inchesapart. In one embodiment, the support material of the device isimpregnated with the surgical material. In one embodiment, the surgicalmaterial forms a separate layer from the support material. In a furtherembodiment, the surgical material may be impregnated in the supportmaterial and also be present as a separate layer.

In one aspect, the device is sterile or sterilizable. The device mayalso be contained in a sterile package.

In one aspect, the device is in the form of a ribbon. The device in theform of a ribbon maybe of any suitable length to width ratio. In oneaspect, the ribbon is of a length to width ratio of from about 10:1 toabout 20:1. In one embodiment, the device in the form of a ribbon isfrom about 10-50 cm long and from about 0.5 to 5 cm wide. In variousembodiments, the ribbon may be from about 10-40, 10-30, or 10-25 cm longand from about 1-2 or 1-3 or 2-5 cm wide. The thickness of the device inthe form of a ribbon maybe from about 0.3 to 5 cm.

In one aspect, the surgical material is an extruded material. In oneaspect, the extruded material is in the form of a ribbon that is fromabout 10-40, 10-30, or 10-25 cm long and from about 1-2 or 1-3 or 2-5 cmwide. The extruded material may be of any suitable thickness. In oneaspect, the thickness of the extruded material is from about 0.1 to 0.5cm, from about 0.1 to 1 cm, from about 0.1 to 2 cm, from about 0.1 to 3cm, from about 0.1 to 4 cm, or from about 0.1 to 5 cm.

In accordance with any of the embodiments of the device describedherein, the surgical material may be suitable for use as a mechanicalhemostat, a bone void filler, a bone graft extender, a bone cement, or atissue adhesive.

In one embodiment, the surgical material is in the physical form of aputty or a paste. In one embodiment, the surgical material is a materialselected from the hemostatic materials described in any of U.S. Pat. No.7,989,000 by Kronenthal (which describes compositions containing a solidparticulate fatty acid salt suspended in a liquid poloxamer along withcertain other excipients); U.S. Pat. No. 5,356,629 by Sander, (whichdescribes a composition containing coated particles ofpolymethylmethacrylate in a matrix of cellulose ether, collagen, orhyaluronic acid); U.S. Pat. Nos. 7,553,913 and 7,829,616 by Wellisz,(which describes hydrophilic, water soluble, waxy compositionscomprising a base of a random copolymer comprising ethylene oxide andone or more other alkylene oxide(s) which maybe mixed with solidparticles); U.S. Pat. No. 7,914,819 by Wen, (which describes a polymericmatrix having a polysaccharide backbone); U.S. Pat. No. 7,074,425 byConstantine, (which describes hydrophilic polyethylene glycol basedcompositions consisting of a mixture of a high and a low molecularweight polyethylene glycol of HLB (hydrophilic/lipophilic balance)greater than 20); and WO 2013067154 by Knaack.

In one embodiment, the support material is a body absorbable ornon-absorbable fabric material. The fabric material maybe woven ornon-woven. In one aspect, the fabric material has an area density offrom about 15 to 35 g/m². In one aspect, the fabric material has an areadensity of from about 18-25 g/m². In one aspect, the fabric material hasan area density of about 16 g/m², 18 g/m², 20 g/m², 22 g/m², 24 g/m², 26g/m², 28 g/m², or 30 g/m².

In one embodiment, the device consists of a 0.3 mm thick optionallypigmented fabric having an area density of about 22 g/m² knitted from3-4 mil monofilament surgical polypropylene fiber. This fabric is cutinto 24 cm by 2 cm pieces, between 2 pieces of which a ribbon ofhemostatic putty, 22 cm long by 1 cm wide by 0.2 cm thick is centrallysandwiched.

In another embodiment, the device consists of a 0.3 mm thick optionallypigmented, absorbable fabric having a^(n) area density of about 22 g/m²knitted from 3-4 mil monofilament polydioxanone fiber. This fabric iscut into 24 cm by 2 cm pieces, between 2 pieces of which a ribbon ofhemostatic putty, 22 cm long by 1 cm wide by 0.2 cm thick is centrallysandwiched.

In another embodiment, the device consists of a 0.3 mm thick pigmentedabsorbable fabric having an area density of about 22 g/m² knitted from3-4 mil monofilament Monocryl fiber. This fabric is cut into 24 cm by 2cm pieces, between 2 pieces of which a ribbon of hemostatic putty, 22 cmlong by 1 cm wide by 0.2 cm thick is centrally sandwiched.

In another embodiment, the device consists of a 0.3-0.5 mm thickoptionally pigmented multifilament fabric having an area density ofabout 22 g/m² knitted from PGLA. This fabric is cut into various shapesand sizes, in which hemostatic putty is impregnated, e.g., 22 cm long by1 cm wide by 0.3-0.5 mm thick.

In one embodiment, the device is sterile and contained within a package.For use, the device is removed from the package, preferably within asterile surgical field. In one embodiment, where the device consists ofa surgical material between two layers of support material, one layer ofthe support material is removed from one side of the surgical materialand discarded. The surgical material, still supported on one side by theremaining layer of support material, is placed on the wound or at thesurgical site and manually pressed into site.

The device as described herein may be used, for example, to achieve oneor more of hemostasis, sealing, pain relief, delivery of therapeuticdrugs, infection control, adhesion, bone growth/healing, fixation, asurgical adhesion barrier, to lend mechanical support, space fillingand/or void filling, depending on the surgical material used.Accordingly, the surgical material of the device may comprise one ormore of an osteoconductive agent, an osteoinductive agent, an analgesic,an antimicrobial agent, an adhesive agent, an anti-tumor therapeuticagent, a hemostatic agent, an anti-inflammatory agent, an anti-surgicaladhesion agent, and/or a hardening material. The surgical material mayalso contain one or more other optional additives as described infra.

In one embodiment, the invention provides methods of sealing ananastomotic wound or surgical site by applying the device to theadjacent surfaces of the anastomosis. In one embodiment, the methodcomprises connecting and sealing a surgical anastomosis, the methodcomprising removing one layer of a support material to expose onesurface of the surgical material, applying the exposed surface of thesurgical material to at least one surface of the tissue anastomosis bypressing the exposed surface of the surgical material onto the surfaceof the tissue anastomosis until it adheres to the tissue, and thenremoving the second layer of support material from the surgicalmaterial, resulting in repair and sealing of the tissue. In oneembodiment, the method comprises wrapping the device around a bloodvessel or cut tissue and applying pressure until the device adheres tothe blood vessel or cut tissue. In one embodiment, the inventionprovides a method for sealing a tissue, the method comprising applyingthe device in the form of an elongated ribbon to at least one cut edgeof a tissue, e.g., a sternum, skull flap, or site of reapproximatedtissues, applying pressure until the device adheres to the cut edge ofthe tissue, and bringing the other edge of the cut tissue into contactwith the device, thereby sealing the tissue. The foregoing methods mayalso include steps of removing one layer of a support material to exposeone surface of a surgical material, applying the exposed surface of thesurgical material to at least one surface of the tissue by pressing theexposed surface of the surgical material onto the surface of the tissueuntil it adheres to the tissue, and then removing the second layer ofsupport material from the surgical material, resulting in repair andsealing of the tissue.

In one embodiment, the invention provides methods of achievingmechanical hemostasis. In accordance with a method for mechanicalhemostasis, the surgical material is pressed into the wound to achievetamponade hemostasis. The term “tamponade” refers to the mechanicalhemostasis occurring when a material is applied to a bleeding surface toocclude the vessels or pores through which blood flows, creating astatic interface between the material and the dammed blood flow. Normalclotting can then occur within this static interface. Thus, inaccordance with this embodiment, the surgical material must be suitablefor use as a tamponade. In the case of hard tissues, such as bone, thematerial must adhere directly to the actively bleeding surface of cutbone, and not be easily dislodged by the force of flowing blood or bysurgical irrigation, and must not be highly water-soluble such thecohesion of the material is lost in the aqueous environment of the woundsite. Once hemostasis is achieved, support material is removed from thetreated surface and discarded so that no support material remains in thewound. In another embodiment, where the surgical material is impregnatedin the support material, the support material containing the surgicalmaterial is pressed directly into the wound, e.g., onto the bleedingwound surface, to achieve tamponade hemostasis and, if absorbable, thesupport material can optionally remain at the surgical site, or it canbe removed and discarded. If the support material is non-absorbable, itis removed and discarded.

In one embodiment, the invention provides a method for mechanicalhemostasis at a wound site, the method comprising wrapping the devicearound a blood vessel or cut tissue and applying pressure until thedevice adheres to the blood vessel or cut tissue. In one embodiment, theinvention provides a method for mechanical hemostasis at a wound site,the method comprising applying the device in the form of an elongatedribbon to at least one cut edge of a tissue, e.g., a sternum, skullflap, or site of reapproximated tissues, and applying pressure until thedevice adheres to the cut edge of the tissue, thereby achievingmechanical hemostasis.

Device with Self-Assembling Peptide-Based Surgical Materials

The surgical material of the devices described herein may consist of oneor more self-assembling peptides, or a composition comprising same,which assemble spontaneously into ordered nanostructures that areadhesive and/or mechanically hemostatic. Examples of suitableself-assembling peptides for use in the surgical materials are describedin U.S. Pat. No. 8,022,178 (Horil et al.) and U.S. Pat. No. 8,299,032(Yokoi et al.), which are incorporated herein by reference in theirentireties. The '178 Patent describes RADA-16 which is a 16-amino acidpeptide commercially available from Innovagen. The '032 Patent describesother peptides containing 12-32 amino acids, one peptide of which iscommercially available from Menicon as PanaceaGel (13 amino acids). BothRADA-16 and PanaceaGel self-assemble in aqueous solution to formcoherent, transparent beta-sheets which then form coherent nanofiberhydrogel networks containing up to 99+% water,

Device with Isocyanate-Based Surgical Materials

The surgical material of the devices described herein may consist of acurable composition, or multiple separate compositions, for example apair of compositions, that are reactive with each other such that whenthe separate curable compositions are combined into a singlecomposition, the single composition begins to cure. In one embodimentwhere the surgical material consists of a single curable composition,cure is initiated when the composition contacts the aqueous environmentof the wound site. In either case, the surgical material (which may alsobe referred to as the curable surgical composition) cures into a fullyhardened polymeric composition, the polymer selected from apolyurethane, a polyureaurethane, a polyetherurethane, or apolyesterurethane, over a period of time at body temperature (i.e.,about 37 C). The period of time ranges from about 5 minutes to 96 hours.

In one embodiment, the surgical material is in a fully or partiallycured state which is hard, relatively rigid and non-pliable, and ispoorly adhesive or non-adhesive, and the surgical material is in contactwith at least one surface of a support material. In the context of thisembodiment, the surgical material, when heated to a temperature ofbetween about 45 C to 75 C, softens and becomes more pliable andadhesive. The surgical material can then be shaped and applied to thewound site where, as it cools, it will return to a hardened, rigid form,non-adhesive (or low adhesive) form. In one embodiment, the supportmaterial is in the form of a mesh having at least one layer of thesurgical material in contact with at least one surface of the mesh.

Each curable composition comprises an isocyanate component and apolyol/polyamine component (which may be referred to simply as“isocyanate” or “polyol/polyamine”). The isocyanate component consistsof an isocyanate monomer, polymer, prepolymer, or combination thereof.The isocyanate component may thus comprise one or more differentisocyanates, as well as an isocyanate in both its monomeric form and itspolymer or prepolymer form. The polyol/polyamine component may also bein the form of a prepolymer, either entirely or partially (such thatsome unreacted polyol/polyamine remains in the composition) The term“isocyanate” is used generically to refer to isocyanates, diisocyanates,and polyisocyanates. The term “polyol” in the context of the“polyol/polyamine component” refers to both diols and polyols. Thus, thepolyol or polyamine component may comprise or consist of one or moredifferent diols, polyols, polyamines, or mixtures of two or more diols,polyols and/or polyamines. The isocyanates and polyol/polyamines thatcan be used in the surgical materials are described in more detailinfra.

In one embodiment, the curable surgical material is able to set andadhere in aqueous environments. By nature, the isocyanate component,even containing hydrolysable linkages, is essentially hydrophobic andwill resist dissolution in aqueous systems. This is true for certaindiamines in this context. It has been found that making the diol morehydrophobic by adding a hydrophobic hydrocarbon-rich residue to apolyol, e.g., glyceryl-1 or 2-monostearate, a more water resistantsystem is obtained. A variation of this embodiment involves thesubstitution of a silicon-based moiety for the hydrocarbon-rich residuealthough this may affect absorbability. Alternatively hydrophobicity andsetting rate in aqueous environments can be improved through the use ofhydrophobic fillers such as insoluble or weakly soluble aliphaticmolecules and salts thereof, including divalent salts, (eg calcium,magnesium, or zinc) of fatty acids. Also useful are cholesterol and itsderivatives, as well as silated derivatives of ceramics or bone (Skimpet al., U.S. Pat. No. 7,270,813) Another embodiment of a waterresistant, settable, surgical material adds a small amount ofhydrophobic isocyanate to the relatively hydrophilic polyol componentresulting in a water-resistant mixture of polyol containing a minoramount of hydrophobic polyurethane prepolymer. In one embodiment, thechain extender does not comprise an amino acid group.

The curable surgical compositions may further comprise an additiveselected from one or more of tocopherol esters (e.g., tocopherylacetate), triglycerides, acetyl triethyl citrate, and fatty acid esters,to aid in handling properties and packaging. In one embodiment, thecurable surgical composition further comprises one or more additivesselected from an antioxidant, an anhydrous particulate material, acolorant, a therapeutic agent, and a radiopaque agent. In oneembodiment, the therapeutic agent is selected from one or more of ananticancer agent, an antimicrobial agent, an anesthetic agent, ananalgesic agent, an anti-inflammatory agent, and an osteogenic agent.

In one embodiment, the curable surgical composition further comprises anosteoconductive component. In one embodiment, the osteoconductivecomponent also confers porosity to the composition and the porosity issufficient to allow the ingress of fluids and/or cells (e.g.,osteoclasts, blood cells) into the composition in situ. In oneembodiment, the osteoconductive component comprises or consists ofparticles of an osteoconductive material, such as particles oftricalcium phosphate or bioglass. The term bioglass refers to a group ofglass-ceramic materials comprising SiO₂, Na₂O, CaOP₂O₅, and combinationsof these.

In one embodiment, porosity is not introduced into the curable surgicalcomposition as it cures by the addition of water or a carboxylic acid,e.g., benzoic acid, into any of the component parts of the composition.In one embodiment, the component parts do not contain either acarboxylic acid or added water such that the only water present duringthe curing reaction is water that may optionally be present at the siteof implantation in the body.

In one embodiment, the fully hardened polyurethane or polyureaurethanecomposition possesses sufficient mechanical properties to be weightbearing, for example for use as a weight-bearing implant in bone, suchas a bone void filler, or a bone cement.

In one embodiment, the curable surgical composition comprises aprepolymer. A prepolymer is a polymer having reactive end groups, e.g.,isocyanate or hydroxyl groups. In one embodiment, the prepolymercomprises an excess of the isocyanate component relative to thepolyol/polyamine component. In one embodiment of a two-componentcomposition, one component comprises a prepolymer and no, Ofsubstantially no, unreacted polyol; and the second comprises or consistsof a hydroxyl terminated prepolymer lacking free isocyanate groups andunreacted polyol or polyamine.

A low molecular weight polymer refers to a polymer having a numberaverage molecular weight in the range of about 500 to 20,000 or 500 to10,000, A prepolymer containing reactive isocyanate end groups isformed, for example, from the initial reaction of an excess ofisocyanate with a limiting amount of polyol or polyamine.

Each of the components may also independently comprise an optionalparticulate material and an optional chain extender, crosslinker, orcurative.

As discussed above, the components of the settable composition areprovided as individual units, each containing reagents in amounts suchthat when the components are mixed together, they form a mixture thatfully reacts or cures into a hardened composition after a period of timeat room or body temperature.

Each composition optionally contains an amount of particulate materialsuspended in the liquid components to form a composition having aputty-like consistency.

In one embodiment, the particulate material is selected from one or moreof a polyurethane, calcium sulfate, calcium phosphosilicate, sodiumphosphate, calcium aluminate, calcium phosphate, hydroxyapatite,demineralized bone, or mineralized bone. Other particulate materials mayalso be used, as described infra.

In one embodiment, the device comprises or consists of a surgicalmaterial and a support material, the surgical material being in the formof a ribbon or sheet and contained between two layers of the supportmaterial (e.g., a top layer and a bottom layer). In one embodiment, thesupport material is body-absorbable and in the form of a microporous ormacroporous mesh, or in the form of a film, as described above. Thesurgical material is in the form of a putty, moldable by hand at roomtemperature. The putty material comprises one or more isocyanates, oneor more polyols or polyamines, and a particulate material in an amountsufficient to impart the viscosity of a hand-moldable putty to thecompositions, for example in an amount of from about 50 to 85 wt % basedon the total weight of the composition. Suitable particulate materialsare described above and it a further aspect, the putty materialcomprises unreacted monomeric isocyanate and a prepolymer consisting ofthe remaining isocyanate reacted with the polyol or polyamine component,such that the composition contains no free (unreacted) polyol orpolyamine. In a specific embodiment, the putty material comprises fromabout 15-40% isocyanate, 0.5-4% polyol/polyamine, and 50-75% particulatematerial. In accordance with this embodiment is provided a method forwound closure, and/or for mechanical hemostasis, the method comprisingremoving one layer of support material from the device to expose asurface of the surgical material, applying the surgical material to thesurface of the wound (e.g., cut bone) with sufficient pressure such thatthe surgical material adheres to the surface of the wound, and removingthe second layer of support material prior to closing the wound. Thesurgical material will cure into a fully hardened polymeric material atthe wound site in situ.

In another embodiment is provided a surgical device consisting of twocomponent devices as described herein. In accordance with thisembodiment, each component device, A and B, comprises or consists of asurgical material and a support material, the surgical material being inthe form of a ribbon or sheet and contained between two layers of thesupport material (e.g., a top layer and a bottom layer). The supportmaterial is preferably body-absorbable and in the form of a microporousor macroporous mesh, or in the form of a film, as described above. Thesurgical material is in the form of a putty, moldable by hand at roomtemperature. The putty material comprises one or more isocyanates, oneor more polyols or polyamines, and a particulate material in an amountsufficient to impart the viscosity of a hand-moldable putty to thecompositions, for example in an amount of from about 50 to 85 wt % basedon the total weight of the surgical material of each component device.The particulate material may be selected from the materials, andcombinations thereof, as described above. The surgical material of eachcomponent device A and B is reactive such that when the surgicalmaterial of component device A contacts that of component device 13, areaction is initiated which results in the curing of A and B into asingle fully cured composition over a period of time.

In one aspect of this embodiment of a surgical device consisting of twocomponent devices, the surgical material of component device A comprises15-40% isocyanate, 0.5-5% polyol, and 50-75% particulate material, basedupon total weight of the surgical material; and the surgical material ofcomponent device B comprises 1-10% of the isocyanate, 3-15% of thepolyol, and 65-95% or 75-85% particulate material, based upon totalweight of the surgical material. In one embodiment, the polyol in A ispresent in a prepolymer with the isocyanate component such that there issubstantially no unreacted polyol in A and the isocyanate component in Bis present in a prepolymer such that there is substantially no unreactedisocyanate in B.

In another aspect of this embodiment of a surgical device consisting oftwo component devices, the surgical material of component device Acomprises 15-40% isocyanate, 0.5-5% of polyol, and 40-85% particulatematerial, based upon total weight of surgical material; and the surgicalmaterial of component device B comprises 1-1.0% isocyanate, 3-1.5% ofpolyol, and 65-95% or 75-85% particulate material, based upon totalweight of the surgical material. In one embodiment, the polyol in A ispresent in a prepolymer with the isocyanate component such that there issubstantially no unreacted polyol in A and the isocyanate component in Bis present in a prepolymer such that there is substantially no unreactedisocyanate in B.

In another aspect of this embodiment of a surgical device consisting oftwo component devices, the surgical material of component device Acomprises 15-50% isocyanate, 0.5-5% polyol, and 40-75% particulatematerial, based upon total weight of the surgical material; and thesurgical material of component device B comprises 1-1.0% isocyanate,3-15% polyol, and 65-85% particulate material, based upon total weightof the surgical material.

In another aspect of this embodiment of a surgical device consisting oftwo component devices, the surgical material of component device Acomprises 20-35% isocyanate, 0.5-5% polyol, and 50-75% particulatematerial, based upon total weight of putty A; and the surgical materialof component device B comprises 1-10% isocyanate, 3-15% polyol, and75-85% particulate material, based upon total weight of the surgicalmaterial,

The Isocyanate Component

In one embodiment, the isocyanate component comprises or consists of anaromatic isocyanate, an aliphatic isocyanate, a cycloaliphaticisocyanate, or an adduct of an isocyanate, or a mixture of any of theforegoing, A mixture refers to a mixture of two or more of theforegoing. For example, the isocyanate component may comprise or consistof a mixture of two or more isocyanates independently selected from anaromatic isocyanate, an aliphatic isocyanate, a cycloaliphaticisocyanate, and an adduct of an isocyanate.

In one embodiment, the isocyanate is an aliphatic isocyanate selectedfrom the group consisting of ethyl lysine diisocyanate, hexamethylenediisocyanate, cyclohexyl diisocyanate.

In one embodiment, the isocyanate component of the curable surgicalmaterial comprises one or more isocyanates that are relativelynon-absorbable. Such surgical materials are particularly suitable tosoft tissue applications (absorbable materials being preferred for hardtissue applications). In one embodiment, the isocyanate is an aromaticisocyanate selected from diphenylmethanediisocyanate (MDI), includingmixtures thereof such as mixtures of 2,4′-diphenylmethanediisocyanateand 4,4′-diphenylmethanediisocyanate isomers (ISONATE 50 OP, DowChemical Co. and RUBINATE 9433, Huntsman Corp.) and its pure4,4-diphenylmethanediisocyanate form (MONDUR M, Bayer AG and RUBINATE44, Huntsman Corp.), In one embodiment, the aromatic isocyanate is oneof the commercially available polymeric isocyanates ISONATE 143L,ISONATE PAPI 901, and ISONATE PAPI 27 (Dow Chemical Co), Theseisocyanates, particularly the diphenylmethane derivatives, generallyresult in non-absorbable or slowly absorbable polyurethanes.

In one embodiment, the surgical material is fully or partiallyabsorbable, and the isocyanate component comprises or consists of[5-[2-[2-(4-Isocyanatobenzoyl)oxypropanoyloxy]-ethoxy]-1-methyl-2-oxo-pentyl]-4-isocyanatobenzoate,or “ALD”. In one embodiment, the two lactyl moieties of ALD each areracemic. Alternatively, these lactyl moieties may both have D or the Lconformations. Alternatively, one lactyl moiety may be D while the otheris L, or one may be D, L while the other is D or L. Such changes instereochemistry may improve the physical and/or biological properties ofthe resulting polymer.

In one embodiment, the adduct of an isocyanate is selected from ahexamethylene diisocyanate trimer (DESMODUR N-3390) and a hexamethylenediisocyanate biuret (DESMODUR N-100) both commercially available fromBayer AG.

In one embodiment, the settable surgical material, which may be formedfrom a polymer selected from a polyurethane, a polyureaurethane, apolyetherurethane, or a polyesterurethane comprises at least onehydrolysable linkage. In one embodiment, the at least one hydrolysablelinkage is derived from glycolic acid, lactic acid, caprolactone, orp-dioxanone. In one embodiment, the at least one hydrolysable linkage isselected from the group consisting of ester, amide, anhydride andsulfonamide linkages between the ester-urethane, urethane- orureaurethane-containing groups. In one embodiment, the materialcomprises one or more glycolyl, lactyl, or caprolactyl hydrolysableester linkages. In one embodiment, the material comprises one or moreethylene glycol, diethylene glycol, propane diol or butane diolhydrolysable ester linkages. In one embodiment, the material comprisesone or more ethylene diamine, propane diamine, butane diamine,hexamethylene diamine and polyalkylene diamine hydrolysable amidelinkages. In one embodiment, the material comprises one or more lactylhydrolysable ester linkages and each asymmetric lactyl moiety present inthe polymer is selected from one or more of the D, the L or the DL(racemic) stereoisomers,

The Polyol/Polyamine Component

The diols, polyols, and polyamines suitable for use in thepolyol/polyamine component of the curable surgical materials are eitherdegradable or non-degradable, or a mixture of the two. As used herein,the term “polyol” is meant to refer generically to diols and polyols,unless indicated otherwise. Generally, absorbable isocyanate basedcompositions are formed by the combination of an excess of theisocyanate component with the polyol/polyamine component. The relativeamounts are calculated as the molar ratio of NCO groups of theisocyanate component (I) to the active hydrogen functional groups (H)(e.g., hydroxyl, amino, and mixtures thereof) of the polyol/polyaminecomponent. Generally, the ratio of polyisocyanate to polyol/polyamine(I:H) is at least 0.5:1. In certain embodiments, the ratio is about 1:1,about 1.5:1, about 2:1, about 3:1, or about 4:1. In other embodiments,the ratio is about 5:1, about 8:1, about 10:1, about 20:1, or about50:1.

In certain embodiments, the polyol/polyamine component is present in anisocyanate prepolymer in an amount of from about 0.5% to about 50% byweight of the prepolymer. In certain embodiments, the polyol/polyaminecomponent is present in an amount of from about 0.5% to 10%, from about10% to 20%, from about 20% to 35%, from about 25% to 40%, or from about35% to 50% by weight of the prepolymer.

Polyols suitable for use include biocompatible, naturally occurringpolyols, synthetic polyols, and mixtures thereof. In certainembodiments, the polyols comprise at least one ester group. In certainembodiments, the polyol comprises 2 to 4 ester groups or 5 to 10 estergroups. In one embodiment, the polyol has two or more hydroxyl groups.Suitable polyols include diols and polydiols having repeating unitscontaining up to about 18 carbon atoms. Examples of suitable diolsinclude 1,2-ethanediol (ethylene glycol), 1,2-propanediol (propyleneglycol), 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol,1,3-cyclopentanediol, 1,6-hexanediol, 1,8-octanediol and combinationsthereof. Examples of preferred polydiols include polyethylene glycolwith molecular weights of from about 500 to about 10000,polytetramethylene ether glycols, polyols derived from glycolide,lactide, trimethylenecarbonate, p-dioxanone and/or caprolactone withmolecular weights of about 500 to about 10000.

In one embodiment, one or more alkylpyrrolidones (see e.g., U.S. Pat.No. 7,955,616) may be added to the polyol component to improve healing.

In one embodiment, the polyol is a synthetic polyol selected from apolycaprolactone polyol, polyester polyols, polyadipate polyols (e.g.,poly(hexane-adipate) dial, poly(butane-adipate) diol,poly(ethylene/propylene-adipate) dial, poly(hexane/adipate/isophthalatediol)), and polyols that have been derived from a synthetic acid (e.g.,isophthalic acid, maleic acid). An example of a suitable biocompatiblesynthetic polyol is a polycaprolactone diol that is commerciallyavailable from Dow Chemical under the trade name TONE 32 B8, or apolycaprolactone co-glycolide or a polycaprolactone co-lactide. Furthernon-limiting examples of suitable synthetic polyols includepoly(oxypropylene) glycols, poly(oxotetramethylene) glycols, andpoly(oxyethylene) glycols. In one embodiment, the synthetic polyol isselected from a polycaprolactone co-glycolide or a polycaprolactoneco-lactide.

In one embodiment, the polyol is a naturally occurring polyol selectedfrom castor oil and lesquerella oil, the polyols that may be obtained bychemical modification of naturally occurring vegetable oils (e.g.,castor oil, olive oil, sesame oil, corn oil), naturally occurring oilsthat have been trans-esterified (e.g., a modified castor oil polyol thathas been prepared by the transesterification reaction of natural castoroil with suitable crosslinkers (e.g., glycerol, trimethylolpropane, andthe like) or with acids (such as adipic acid), and naturally occurringoils that have been hydrogenated. Further non-limiting examples ofsuitable naturally occurring polyols include the commercially availablecastor-oil-based polyols CASPOL5001, CASPOL1962, and CASPOL5004 (allavailable from CasChem., Inc.). In certain embodiments, the polyol isnot a naturally occurring polyol such as castor oil and lesquerella oil.

In certain embodiments, an isocyanate prepolymer is combined with apolyamine to form a poly(urethane-urea). The polyamine may be a primaryor secondary di-amine, or a hindered amine. Non-limiting examples ofsuitable polyamines include, hindered diamine (e.g., isophorone diamine,“IPDA”), 1,4-cyclohexyl diamine, 1,3-pentane diamine, and aliphaticsecondary diamines, and mixtures thereof. In certain embodiments of thepresent invention, aliphatic diamines and cycloaliphatic diamines may beparticularly suitable, and may offer improved biocompatibility.Commercially available examples of suitable polyamines include CLEARLINK1000 (Dorf Ketal).

Amines including diamines that may be suitable for use in thepreparation of polyurea and polyureaurethanes include but are notlimited to polyethyleneimines, PEG amines with weight average molecularweights from about 500 to about 5,000, polyoxypropylenediaminesavailable under the tradename JEFFAMINES (Huntsman Corporation, Houston,Tex.) and polyetherdiamines in general, spermine, spermidine,hexamethylenediamine, octamethylenediamine, decamethylenediamine,dodecamethylenediamine, hexadecamethylenediamine,octadecamethylenediamine, polyamidoamine dendrimers, dextrans,PEG-dextran conjugates, cysteines, proteins and peptides containingamines, non-biologically active symmetrical and asymmetrical diaminocompounds containing saturated and unsaturated, substituted andunsubstituted alkyl, aryl and alkylaryl groups having from about 2 toabout 18 carbon atoms. Further, the diamino compound can be synthesizedcontaining a hydrolyzable link such as one or more ester groups toaccelerate the rate of polymer degradation (absorption) in the body. Thefollowing structure exemplifies this concept for hexamethylenediamine:H₂NCH₂CH₂CH₂COOCH₂CH₂NH₂.

In certain embodiments, the polyol comprises 2 to 4 ester groups or 5 to10 ester groups. Suitable polyols have at least two hydroxyl groups. Incertain embodiments, the polyol has three or more hydroxyl groups makingthem crosslinkers.

The Chain-Extender/Crosslinker Component

In certain embodiments, one or more optional chain extenders orcrosslinkers is incorporated in the curable surgical materials. Incertain embodiments, only a chain extender is present. In otherembodiments, both a chain extender and a crosslinker are present. In oneembodiment, the one or more chain extenders is a low molecular weightpolyhydroxyl- and/or polyamine-terminated compound having a molecularweight in the range of 10 to 500 Daltons and a functionality of at leasttwo. In certain embodiments, the chain extender is a short-chain diol ordiamine. In a particular embodiment, the chain extender or crosslinkeris selected from glycerol, 1,4 butanediol, 1,6-hexanediol, diethyleneglycol, and combinations thereof. Chain extenders having a functionalityof three or more than three are also referred to as crosslinkers. Incertain embodiments, the compositions of the invention are formedwithout crosslinkers and the compositions of the invention are notcrosslinked. In other embodiments, the compositions of the invention areformed with one or more crosslinkers. The degree of crosslinking can becontrolled, for example, by varying the amount of crosslinker present.

In certain embodiments, the chain-extender or crosslinker is present inan isocyanate prepolymer in an amount in the range of about 5% to about80% by weight of the isocyanate prepolymer. In certain embodiments, thechain-extender or crosslinker is present in an amount of from about 5%to 20%, about 20% to 30%, about 30% to 40%, about 40% to 50%, about 50%to 60%, from about 60% to 70%, or from about 70% to 80% by weight of theisocyanate prepolymer.

The chain extender may be degradable or non-degradable. Preferably, atleast one degradable chain extender is used. Suitable degradable chainextenders for use in the present invention are described in U.S. PatentApplication Serial No. 2009/0082540, which is incorporated herein byreference. In one embodiment, the at least one degradable chain extenderis HOCH₂CO₂CH₂CH₂OH or HOCH₂CO₂CH₂CH₂O₂CCH₂OH.

Other suitable chain-extenders or crosslinkers include natural orsynthetic aliphatic polyols. Suitable polydiols for use in the presentinvention include diol or diol repeating units with up to 8 carbonatoms. Non-limiting examples include 1,2-ethanediol (ethylene glycol),1,2-propanediol (propylene glycol), 1,3-propanediol, 1,4-butanediol,1,5-pentanediol, 1,3-cyclopentanediol, 1,6-hexanediol,1,4-cyclohexanediol, 1,8-octanediol and combinations thereof.

In other embodiments, the chain extender is a polyol selected frompolyethylene glycol and polypropylene glycol having molecular weights of500-10000 Daltons. Other examples include CASPOL1962 and CASPOL5004. Incertain embodiments the preferred polydiols include polydiols selectedfrom polyethylene glycol and polypropylene glycol with molecular weightsof 500-10000. In some embodiments, the crosslinker is a non-absorbablecrosslinker selected from triethanolamine (TEA), trimethylolpropane, andQUADROL (BASF Corp.). In some embodiments, the chain-extender is anon-degradable chain extender selected from 1,4-butanediol,1,6-hexanediol, and diethylene glycol. The chain-extender or crosslinkermay be present in an isocyanate prepolymer in an amount in the range ofabout 10% to about 80% by weight of the isocyanate prepolymer.

Water

In certain embodiments, the curable surgical material contains no addedwater. In some embodiments, the material is anhydrous. In certainembodiments where there is no added water, water may nevertheless bepresent in small amounts. For example, certain commercially-availablepolyols comprise a mixture of the polyol and a small amount of water. Inaddition, certain optional particulate materials as described herein,such as calcium carbonate, may comprise bound water. Formulating thecompositions in an atmosphere that contains moisture may also result inthe incorporation of water. In certain embodiments, the compositions areprepared under a nitrogen purge that comprises a desired amount ofmoisture, thereby controlling the water content of the compositions. Inother embodiments, water may be added to the compositions during theprocess of their formation from the component parts. In otherembodiments, the compositions are prepared under essentially water-freeconditions with anhydrous components such that the resultingcompositions are essentially anhydrous.

In certain embodiments, water is present in the compositions being madein an amount from at least about 0.01% to about 3% by weight of thecomposition. In certain embodiments, water is present in an amount offrom about 0.05% to 1%, from about 0.05% to 1.5%, from about 0.1% to 1%,from about 0.1% to 1.5%, from about 0.1% to 2%, from about 1% to 2%, orfrom about 2% to 3%. In one embodiment, the amount of water is less than3%, less than 2%, less than 1%, less than 0.5%, or less than 0.05%

Particulate Materials

The surgical material of a device as described herein, including thesurgical materials comprising self-assembling peptides and the curablesurgical materials described above, may contain optional particulatematerials. In one embodiment, the particulate material is anosteoconductive material. In certain embodiments, the particulatematerial supports or promotes the growth of bone at the applicationsite. In one embodiment, the particulate material is non-resorbable. Incertain embodiments, the mean particle size of the optional particulatematerial is in the micron or submicron range. In one embodiment, themean particle size is from about 0.001 to 0.100 microns, from about0.100 to 5 microns, from about 5 to 100 microns, from about 5 to 500microns, or from about 500 to 2000 microns.

In one embodiment, the optional particulate material is a carbonate orbicarbonate material. In one embodiment, the carbonate or bicarbonatematerial comprises or consists of one or more of calcium carbonate,magnesium carbonate, aluminum carbonate, iron carbonate, zinc carbonate,calcium bicarbonate, and sodium bicarbonate. In one embodiment, theoptional particulate material comprises or consists of bone (e.g.,demineralized bone, bone morphogenetic protein, allograft bone, and/orautogenous bone), calcium phosphate, siliconized calcium phosphate,substituted calcium phosphates (e.g., with magnesium, strontium, orsilicate), calcium pyrophosphate, hydroxyapatite, polymethylmethacrylate, glass-ionomer, absorbable phosphate glass, calciumsulfate, tricalcium phosphate (e.g., beta tricalcium phosphate), or anycombination of the foregoing. Other examples include one or more polyether ether ketones (e.g., PEEK), REPLACE (Cortek, Inc.), EXPANCEL (AkzoNobel). In other embodiments, the particulate material is a ceramic suchas substituted calcium phosphates (e.g, silicate, strontium or magnesiumsubstitution) or a glass such as bioglass. In one embodiment, theparticulate material comprises or consists of one or more of calciumsulfate, calcium phosphosilicate, sodium phosphate, calcium aluminate,calcium phosphate, hydroxyapatite, demineralized bone, or mineralizedbone.

The optional particulate material, when present, may comprise any one ormore of the materials listed in the embodiments above. In oneembodiment, the particulate material, if present in the composition,does not comprise calcium carbonate. In one embodiment, the particulatematerial may be polymeric such as a polyurethane.

In one embodiment, the particulate material is present in an amount offrom about 0.01% to about 10% by weight of the composition. In certainembodiments, the optional particulate material is present in an amountof 0.10% to 10%, 1% to 10%, or 5% to 10%. In other embodiments, theoptional particulate material is present in an amount of from about 10%to about 20% by weight of the composition, or from about 20% to 30%,about 30% to 40%, about 40% to 50%, about 50% to 60%, about 60% to 70%or about 70% to 80% by weight of the composition.

In one embodiment, the particulate additive material is graphene(available from Applied Graphene Materials and Thomas Swan, Ltd.), asingle atomic layer of graphite that is electrically conductive, highlyelastic, is about 100 times stronger than steel and which may be ofvalue improving the quality of tissue healing and new bone stimulation.

Other Optional Additives

The surgical material of a device as described herein, including thesurgical materials comprising self-assembling peptides and the curablesurgical materials described above may also contain one or more optionaladditives.

The surgical materials may also optionally comprise one or more “cellopeners.” Non-limiting examples include ORTOGEL501 (Goldschmidt) andX-AIR (Specialty Polymers & Services). In certain embodiments, the cellopeners are present in an amount in of from about 0.1% to 5% by weightof the composition. In one embodiment, the cell openers are present inan amount in of from about 1% to 2% or 1% to 3% by weight of thecomposition. Optional additives can be added to the magnesium basedsection but for the malonate/cyanoacrylate section, no active hydrogenatoms can be present including those in water because they will initiatepolymerization.

The surgical material may also optionally comprise one or moretherapeutic agents. In one embodiment, the one or more therapeuticagents are selected from an anti-cancer agent, an antimicrobial agent,an antibiotic, a local anesthetic or analgesic, a statin and ananti-inflammatory agent. In one embodiment, the antibiotic is selectedfrom a broad spectrum antibiotic, such as gentamicin, clindamycin, anderythromycin, or a gram positive and gram negative family antibioticsuch as an ampicillin and a cephalosporin. In one embodiment, the localanesthetic or analgesic is selected from lidocaine, bupivacaine,tetracaine, and ropivacaine. In one embodiment, the local anesthetic oranalgesic is selected from lidocaine, benzocaine and fentanyl (a potentnon-opioid anesthetic). In one embodiment, the one or moreanti-inflammatory substances is selected from a non-specificanti-inflammatory such as ibuprofen and aspirin, or a COX-2 specificinhibitor such as rofecoxib and celeboxib.

In one embodiment, the surgical materials may further comprise one ormore of an antioxidant, a colorant, a steroid, calcium stearate,tocopheryl acetate, and triacetin. In one embodiment, the antioxidant isselected from IRGANOX 1010 and IRGANOX 1035 (Ciba Geigy), and CYANOX1790 and CYANOX 2777 (Cytec Industries). In certain embodiments, theantioxidant is present in an amount of from about 0.01% to 0.5% byweight of the composition. In one embodiment, the steroid is asteroid-based compound, such as an intracellular messenger, effective tomodulate the rate of tissue growth, including bone growth. In oneembodiment, the compositions further comprise one or more growthfactors, for example BMP-2, BMP-7, PDGF, EGF, etc.

In one embodiment, the surgical material comprises one or more ofcalcium stearate, tocopheryl acetate, and triacetin, each present in acomponent putty of the composition in an amount ranging from 0.1 to 7%based upon the weight of the component putty. Non-limiting examples ofcolorants that may be included in the compositions are gentian violet,D&C Violet #2, and D&C Green #6.

EXAMPLES

The following non-limiting examples are provided to further illustrateembodiments of the invention disclosed herein. It will be appreciated bythose of skill in the art that the techniques disclosed in the examplesthat follow represent approaches that have been found to function wellin the practice of the invention and thus can be considered toconstitute examples of modes for its practice. However, those of skillin the art will, in light of the present disclosure, appreciate thatmany changes can be made in the specific embodiments that are disclosedand still obtain a like or similar result without departing from thespirit and scope of the invention.

Example 1 (Soft Tissue)

To provide reinforcement to weakened soft tissue, a monofilamentpolypropylene mesh with a pore size of 1 mm was spray coated with asolution of 40% ALD, 20% Polyethylene glycol (300) and 40% methylenechloride. Following evaporation of the methylene chloride solvent, thegel was sufficiently coherent to hold the mesh in place until it wasincorporated into normal body proteins. Its absorption rate was notdetermined.

Example 2 (Soft Tissue)

To provide hemostasis to soft tissue, a monofilament polylactide meshwith a pore size of 10 micron was spray coated with a solution of 40%ALD 20% Polyethylene glycol (300), 10% chitosan (microparticulate) and30% methylene chloride. Following evaporation of the methylene chloridesolvent, the implant was hemostatic to lacerated soft tissue uponapplication. Its absorption rate was not determined.

Example 3 (Soft Tissue, Self-Assembling Peptides)

To provide reinforcement to weakened soft tissue, a 3.5 square inchknitted monofilament polypropylene mesh was placed on the surface of thetissue to be reinforced, in this case muscle, and coated with 5.75 ml.of a 0.5% aqueous solution of PanaceaGel which formed a transparent gelwithin 2 minutes following application. The gel was sufficientlycoherent to hold the mesh in place until it was incorporated into normalbody proteins. Its absorption rate was not determined.

Example 4 (Hard Tissue, Self-Assembling Peptides)

To provide hemostasis to a bleeding bone surface, 2.5 ml. of a RADA-16aqueous solution (0.8%) was applied to a bleeding bone surface andcoagulated into a transparent gel which stopped the blood flow in 17seconds. The gel was absorbed within 72 hours.

Example 5 (Hard Tissue, Isocyanate-Based Surgical Material)

In order to reapproximate adjacent segments of bone tissue, a deviceconsisting of a ribbon of putty composed of 37% ALD, 2.5% PCL900, 6.5%Triacetin and 54% hydroxyapatite sandwiched between two layers ofpolyvinylchloride (PVC) non-porous film was used. One layer of PVC filmwas removed from the device to expose a surface of the putty. The puttyedge was pressed into one of the two sternal edges following a medialsternotomy. The second PVC layer was then peeled away, leaving the puttyadhered to the edge of the sternum. This action was repeated for thesecond sternal edge. The sternum was then wired closed, excess putty wasremoved and the entire sternum was incubated at 37 C in phosphatebuffered saline. Following 24 hours, the wiring was removed and theputty material was found to have cured into a fully hardened material atthe wound site in situ that was sufficiently coherent to hold thesternal edges together. Its absorption rate was not determined.

Example 6 (Hard Tissue, Isocyanate-Based Surgical Material)

In order to reapproximate adjacent segments of bone tissue, a deviceconsisting of a ribbon of putty composed of 37% ALD, 3% PCL300, and 60%hydroxapatite sandwiched between two layers of polyethylene (PE)non-porous film was used. One layer of PE film was removed from thedevice to expose a surface of the putty. The putty edge was pressed intothe edges of a cranial skull flap. The second PE layer was then peeledaway, leaving the putty adhered to the edge of the skull flap. The skullflap was manually reapproximated into the surrounding cranium, excessputty was removed and the cranium was incubated at 37 C in phosphatebuffered saline. Following 24 hours, the putty material was found tohave cured into a fully hardened material at the wound site in situ thatwas sufficiently coherent to hold the skull flap in place. Itsabsorption rate was not determined.

Example 7 (Hard Tissue, Isocyanate-Based Surgical Material)

In order to reapproximate adjacent segments of bone tissue, a deviceconsisting of A) a ribbon of putty composed of 37% ALD, 2.5% PCL900,6.5% Triacetin and 54% hydroxapatite sandwiched between two layers ofpolyvinylchloride (PVC) non-porous film and B) a second ribbon of puttycomposed of 5% ALD, 8% PCL900, 4.5 Tocopherol Acetate 3.5% Triacetin and79% calcium stearate sandwiched between two layers of polyvinylchloride(PVC) non-porous film, was used. One layer of PVC film was removed fromthe device to expose a surface of the putty A. The putty edge waspressed into one of the two sternal edges following a medial sternotomy.The second PVC layer was then peeled away, leaving the putty adhered tothe edge of the sternum. This action was repeated for the second sternaledge using the films sandwiching the ribbon of putty B. The sternum wasthen wired closed, excess putty was removed and the entire sternum wasincubated at 37 C in phosphate buffered saline. Following 24 hours, thewiring was removed and the putty material was found to have cured into afully hardened material at the wound site in situ that was sufficientlycoherent to hold the sternal edges together. Its absorption rate was notdetermined.

EQUIVALENTS

Those skilled in the art will recognize or be able to ascertain using nomore than routine experimentation, many equivalents to the specificembodiments of the invention described herein. Such equivalents areintended to be encompassed by the following claims.

All references cited herein are incorporated herein by reference intheir entirety and for all purposes to the same extent as if eachindividual publication or patent or patent application was specificallyand individually indicated to be incorporated by reference in itsentirety for all purposes.

The present invention is not to be limited in scope by the specificembodiments described herein. Indeed, various modifications of theinvention in addition to those described herein will become apparent tothose skilled in the art from the foregoing description and accompanyingfigures. Such modifications are intended to fall within the scope of theappended claims.

What is claimed is:
 1. A surgical device in the form of a fabric or film that provides mechanical assistance for the application of a surgical material to a wound or surgical site, the device comprising a ribbon or sheet of surgical material selected from the group consisting of a hemostatic material, a hone void filler, a bone graft extender, a bone cement, a surgical sealant, a surgical adhesion barrier, an anti-surgical adhesion agent, an antimicrobial, an analgesic, an antineoplastic, an anti-inflammatory, a radiopaque, an osteoconductive material, an osteoinductive material, and any combination thereof, and a support material selected from the group consisting of a fabric or a film material, wherein the support material comprises two separate layers that surround the surgical material, wherein the surgical material is a composition in the form of a putty that is moldable and shapeable at room temperature and suitable for the mechanical hemostasis of hard tissue.
 2. The surgical device of claim 1, wherein the surgical material is a high viscosity or a low viscosity material.
 3. The surgical device of claim 1, wherein the surgical material is a composition in the form of a paste.
 4. The surgical device of claim 1, wherein the support material is constructed from a non-absorbable fabric or a non-absorbable polymeric film material of low surface energy.
 5. The surgical device of claim 4, wherein the fabric or film material is dyed or pigmented.
 6. The surgical device of claim 5, wherein the fabric is non-absorbable and is knitted or woven.
 7. The surgical device of claim 4, wherein the polymeric film material is constructed from one or more of a polyurethane, a poly(propylene), a poly(tetrafluorethylene), or a polysiloxane.
 8. The surgical device of claim 1, wherein the surgical material is non-body absorbable, body absorbable, or partially body absorbable.
 9. A method for mechanical hemostasis of actively bleeding soft or hard tissue, the method comprising applying an exposed surface of surgical material present in the surgical device of claim 1 to at least one surface of the bleeding tissue by pressing the exposed surface of the surgical material onto the surface of the tissue until is adheres to the tissue, thereby resulting in mechanical hemostasis of the bleeding soft or hard tissue.
 10. The method of claim 9, wherein, when the bleeding tissue is a soft tissue, the surgical material is a low viscosity material.
 11. The method of claim 9, wherein prior to use, a first layer of the support material is removed from the surgical material to produce the exposed surface.
 12. The method of claim 11, wherein following application, the second layer of the support material is removed from the surgical device following adhesion of the surgical material.
 13. A method for connecting and sealing a surgical anastomosis, the method comprising applying an exposed surface of the surgical sealant present in the surgical device of claim 1 to at least one surface of the tissue anastomosis by pressing the exposed surface of the surgical material onto the surface of the tissue anastomosis until it adheres to the tissue, thereby resulting in connection and sealing of the tissue.
 14. The method of claim 13, wherein prior to use, a first layer of the support material is removed from the surgical material to produce the exposed surface.
 15. The method of claim 14, wherein following application, the second layer of the support material is removed from the surgical device following adhesion of the surgical material.
 16. A method for prevention of surgical adhesions of soft tissue, the method comprising applying an exposed surface of surgical material present in the surgical device of claim 1, wherein the surgical material comprises a surgical adhesion barrier or an anti-surgical adhesion agent, to at least one surface of the soft tissue by pressing the exposed surface of the surgical adhesion barrier or the anti-surgical adhesion agent onto the surface of the soft tissue until is adheres to the soft tissue, thereby preventing the formation of surgical adhesions on soft tissue.
 17. The method of claim 16, wherein, when the bleeding tissue is a soft tissue, the surgical material is a low viscosity material.
 18. The method of claim 17, wherein prior to use, a first layer of the support material is removed from the surgical material to produce the exposed surface. 